Registration Dossier

Toxicological information

Endpoint summary

Currently viewing:

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
1 012
Study duration:
subacute
Species:
rat
Quality of whole database:
Adequate information is available for a representative substance to characterise the reproductive hazards of these streams.
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Non human studies

The available data on the specific component toluene does not reveal any reproductive toxicity of a severity that would warrant classification.

Two key studies are identified for toluene:

Roberts et al (2003) conducted a combined two-generation fertility and teratogenicity inhalation study in rats. Exposure to toluene was at 0, 100, 500 or 2000 ppm 6 h/day, 7 days/week during an 80 day pre-mating period and 15 day mating period. Females were further exposed during gestation (GD 1-20) and lactation (LD 5-21). Toluene exposure did not induce adverse effects on fertility and the NOAEC for effects on fertility was 2000 ppm (7500 mg/m3), the highest dose tested.

In the study of Ono et al rats were exposed to toluene vapour at 600 and 2000 ppm for 6 h/day, and effects on their fertility were investigated. Females were exposed from 14 days before mating until day 7 of gestation. Males were exposed for a total of 90 days, including the mating period; treatment was begun 60 days before pairing, and toxicity with respect to testicular and reproductive functions was examined. Although no abnormalities were seen in mating behaviour or fertility in the males exposed to 2000 ppm decreases in the weights of the epididymides and sperm count were observed. The NOAEC for effects on male fertility was 600 ppm (2261 mg/m3).

Human information

There are no human data for low benzene naphtha streams.

For toluene the EU RAR (2003) concluded “In humans, no studies of effects of toluene on sperm count were found. Limited data in humans have not shown indication of effects on fertility in men or menstrual function in women”. Consequently a value of 2261 mg/m3 from the Ono study will be taken into consideration for classification.

References

EU RAR (2003). Toluene risk assessment report. European Union Risk Assessment Report, Volume 30.

Ono A, Sekita K, Ogawa Y, Hirose A, Suzuki S, Saito M, Naito K, Kaneko T, Furuya T, Kawashima K, Yasuhara K, Matsumoto K, Tanaka S, Inoue T and Kurokawa Y (1996). Reproductive and developmental toxicity studies of toluene II. Effects of inhalation exposure on fertility in rats. Journal of Environmental Pathology Toxicology and Oncology 15, 9-20.

Roberts LG, Bevans AC and Schreiner CA (2003). Developmental and reproductive toxicity evaluation of toluene vapor in the rat. 1. Reproductive toxicity. Reproductive Toxicology, 17, 649-658. Testing laboratory: International Research and Development Corporation, Mattawan, MI, USA.


Short description of key information:
It is recognised that there is a data gap for a multi-generation study (REACH reference 8.7.3). The applicant submits that this study does not need to be conducted since data are available on a low benzene naphtha stream, CAS 68476-55-1 and the component substance, toluene, which are adequate for the purposes of classification and labelling and/or risk assessment of the UVCB substances included in this category.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
1 012
Study duration:
subacute
Species:
rat
Quality of whole database:
Adequate information is available for a representative substance to characterise the reproductive hazards of these streams.
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Non-human information

 

Toluene (Classification: Category 2, H361d): There is no evidence that toluene produces malformation in animals or humans. There is some evidence of developmental toxicity (lower body weight at birth and delayed vaginal opening) at toluene exposure concentrations ≥ 1000 ppm, concentrations which are associated with slight maternal toxicity. The NOAEC for developmental and maternal effects is 600 ppm (2261 mg/m3) (Thiel and Chahoud, 1997).


Justification for selection of Effect on developmental toxicity: via inhalation route:
Results from a reproduction/developmental toxicity screening study (OECD 422) conducted on a representative stream showed no evidence of effects on foetal development at the highest concentration tested (1012 ppm). The key marker substance toluene is classified for effects on development, and streams containing >3% require classification under GHS.

Justification for classification or non-classification

There are sufficient data available on the component substance, toluene, to conclude that streams within this category that contain less than 3% toluene are not reproductive toxicants and do not require a label for this endpoint.

On the basis of possible effects on development in animals studies with toluene, low benzene naphtha streams which contain ≥ 3% toluene should be classified Category 2, H361d according to CLP.